Psoriasis is a type of chronic disease associated with various changes ,so they're many mechanisms and theories approved to help us to understand this autoimmune disease . Many lines of treatments are approved as a result of these theories .
Metabolic changes
The saturated fatty acids (SFA) –palmitate and stearine- are highly increased in the blood samples of psoriatic patients in comparison to the levels of poly un saturated fatty acids (EFA)-linoleic and arachidonic, wich play an important role as structral compounds of membrane cell phospholipids. EFAs play an important role in different metabolic pathways . It is suggested that membrane phospholipid compounds differ in patients suffering from psoriasis combined with a lower content of essential fatty acids compared to saturated fatty acids. This leads to changes in the lipid surroundings of membrane proteins, which are mainly receptors and enzymes. The changes refer to the tertiary and 4th structure of the proteins. This explains the altered activity of certain receptors which on their part influence the activity of phospholipase A2 and phospholipase C. Those are the main enzymes involved in the metabolism of the phospholipids and their different metabolite pathways. The authors of this hypothesis believe that either the reduced intake of essential polyunsaturated fatty acids or the impaired EFA/SFA ratio intake in genetically predisposed individuals cause increased synthesis of arachidonic acid and its inflammatory metabolite substances, respectively. However, the correction of the polyunsaturated fatty acid intake to proper quantities could have formed anti-inflammatory mediators- PG E1 and PG E3, for example.
The idea of the introduction of polyunsaturated fatty acids in everyday diet as a psoriasis therapy is based on the epidemiological characteristics of the disease and particularly on the low incidence in Eskimo population. Obviously, the rich content of polyunsaturated fatty acids in fish- the most common food product in Eskimo diet- can be determined as a preventing factor. Surely, the proper everyday intake of essential fatty acids could change the lipid surrounding of membrane proteins, thus modulating their conformation and activity. Avoiding the oversupply of arachidonic acid, and reaching appropriate balance in the EFA/SFA ratio, proper synthesis of anti-inflammatory mediators can be obtained.
Theproper EFA/ SFA intake harmonizes the impaired Th1/Th2 balance and increases the resistance towards exogeneous inflammatory factors (bacterial, viral, etc.) that often trigger certain chronic relapsing dermatoses including psoriasis
Increased levels of level of leukotriene B4 which is a potent chemotactic factor which helps to aggravate the inflammation and complication of the disease . we know that leukotrienes are generated from lipoxygenase enzyme and It's reported that It’s associated also with heterogenous distribution of lipoxygenase products in psoriatic skin lesions.
The content of each of the identified lipoxygenase products was higher in the superficial part of the biopsy specimen consisting of approximately two-thirds of the epidermis plus papillary dermis than in the lower part consisting of approximately one-third of the epidermis plus some reticular dermis. Also, there was a great variation from one anatomical region to another within the same patient. Because these lipoxygenase products possess different biological activities, the variation in their occurrence may be important for understanding their potential role in psoriasis
cAMP deficiency. cAMP is a nucleotide, which plays an important role in the processes of cell differentiation, hormonal synthesis and stimulation of glucogenolysis. The cAMP deficiency in the inflamed skin lesions increases the cell permeability and distribution of lysosome enzymes in the corneal layer. The level of cGMP and the cGMP/cAMP ratio is significantly higher in the psoriatic lesions.
Decreased synthesis of chalones. The chalones are proteins restricting cell divisionrate. Their effect can be regulated by adrenaline with which they activate adenylatecyclase, thus increasing the level of cAMP. The reduced quantity of chalones in the psoriatic lesion leads to accelerated cell proliferation and regeneration time reduction.
Psoriasis also causes alterations in epidermal keratin expression. The keratin expression in the basal layer is similar between the healthy and psoriatic skin as they both express K5 and K14 keratins. In healthy skin suprabasal keratinocytes express differentiation specific keratins 1 and 10, but in psoriatic suprabasal keratinocytes their expression is downregulated and hyperproliferative keratins 6 and 16 are expressed instead. In addition, keratin 17 expression is abundant in psoriatic lesions
In addition, it is inadequate to consider psoriasis only as a disease of the skin as in fact, psoriasis is associated with many systemic disorders like Crohn’s disease, Both psoriasis and Crohn’s patients are characterised by highlevels of TNF-α and inflammation of stratified epithelia metabolic syndrome, type 2 diabetes and depression. The disease risk can also vary according to the severity of psoriasis. This is seen with psoriasis and cardiovascular disease: patients with mild psoriasis do not have increased risk, but if psoriasis is moderate or severe the relative risk for cardiovascular disease is almost three-fold. In addition, psoriasis associates with cancers such as lymphoma, but it remains unsolved whether the relation is with the disease itself or with the treatments used like photochemotherapy
Integrin and corneodesmosin are two proteins that are important in keratinocyte adhesion and differentiation; it appears that in lesional skin integrin has altered cytoskeleton associations, whereas corneodesmosin is over-expressed . It is not clear yet whether these abnormalities are responsible for reduced keratinocyte adhesion and therefore excessive scaling, or, on the contrary, cause increased inter-cellular adherence with subsequent formation of clumps of keratinocytes (scale) which fail to differentiate
Immunological changes
Psoriasis is an autoimmune disorders or a T-helper (Th1) / (Th17) immune dysfunction[53] .T-cell activation, TNFα, and dendritic cells are pathogenic factors stimulated in response to a triggering factor, such as a physical injury, inflammation, bacteria[52] (A self-peptide cross-reacting with streptococcal M protein bacteria-derived superantigens is one of the candidates as streptococcal infections precede 90% of psoriasis type I cases) virus retrovirus (human immunodeficiency virus 1[9]), and human papilloma virus, or withdrawal of corticosteroid medication.
Initially, immature dendritic cells in the epidermis stimulate T-cells from lymph nodes in response to as yet unidentified antigen stimulation . Dendritic cells (DC) act as antigen-presenting cells (APC) to initiate the immunoresponse after stimulation by an as yet unknown signal. Activated DCs migrate to lymphatic tissue and secrete chemokines to attract naive T lymphocytes, which are then activated and differentiated to Th1 and Th17 type cells. Movement of the activated T lymphocytes from the periphery to the skin is elementary for the plaque to develop. the dendritic cells (DC) are the most common type of antigen-presenting cells. Antigens are presented on the DC surface usually as MHC class II molecules, which can be recognized by T cell receptor of CD4+ T cells. In addition DCs can present antigens on MHC class I molecules, which lead to the activation of CD8+ T cells. DCs also enhance the production of adhesion and co-stimulatory molecules to facilitate its interaction with T cells. The antigens behind the process are not known
Psoriasis is commonly considered to be a Th1 type disease and cytokines of the pathway, including IL-2, IL-12, IFN- γ and TNF-α, are abundantly found in psoriasis plaques Interleukin-2 is a T cell growth factor, which promotes T cell function, as well as stimulates natural killer cell activity, and promotes production of a wide variety of cytokines Interferon γ is an important immuneregulator and also has antiproliferative properties
In psoriatic skin IL-23 is overproduced by DCs and keratinocytes and promotes Th 17type T cells‘ survival and the production of IL-17 and IL-22, which are also considered to be significant in psoriasis . Interleukin 17 promotes accumulation of neutrophils, dendritic cells and T cells and also has an impact on barrier function. Interleukin-22 triggers keratinocyte hyperproliferation and down regulates genes associated with keratinocyte differentiation, which are functional aspects relevant for the pathogenesis of psoriasis.
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